Effect of Parkinson-related PINK1 defect on human astrocytes
| Autor: | Yi-Ling Chang, 張依琳 |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, characterized by the selective and progressive loss of dopaminergic neurons in the substantia nigra. The pathogenic mechanism of PD is still unclear. Mutations in the human, PTEN-induced putative kinase 1 (PINK1) is the second most common causative gene of recessive familial PD. PINK1 protein was proved to be protective for oxidative stress and neuronal apoptosis. Glial cells play an important role in the homeostasis of the microenvironment which is supportive for the survival of neurons. Up to date, the function of the PINK1 protein in the glial cells has not been studied yet. To address this issue, we used human astrocytoma cell line (A172) and transfected PINK1 shRNA and PINK1 mutnats mimicking the reduced expression of functional PINK1 protein. Silencing the expression of PINK1 protein potentiated the H2O2–induced reduction of mitochondria membrane potential, and also enhanced H2O2 and MPP+-induced increase of ROS production. Furthermore, while analyzed using MTT assay, decrease of the cell viability following exposure to H2O2 was observed in the PINK1 shRNA transfected astrocytoma cells. PINK1 mutant (G309D or K219A) also decreased the cell viability following exposure to H2O2. Glial cell derived nerve growth factor (GDNF) which is important in nourishing the neurons, was not reduced in those glial cells with reduced expression of PINK1. Our results show that PINK1 can prevent astrocytes from oxidative stress and cell death. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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